CN108727216A - Method for synthesizing α -diazo ester compound by using microwave under normal pressure - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 12
- 230000002194 synthesizing effect Effects 0.000 title abstract description 3
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- -1 ester compounds Chemical class 0.000 claims abstract description 11
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims abstract description 6
- 238000006276 transfer reaction Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 75
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 150000001540 azides Chemical class 0.000 claims description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 239000012954 diazonium Substances 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 229940125782 compound 2 Drugs 0.000 claims description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000010304 firing Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000012973 diazabicyclooctane Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 229940126086 compound 21 Drugs 0.000 claims 2
- 238000010189 synthetic method Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 abstract description 31
- 239000002994 raw material Substances 0.000 abstract description 12
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 abstract 2
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- 238000000926 separation method Methods 0.000 description 19
- 235000019270 ammonium chloride Nutrition 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 238000001035 drying Methods 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 239000003208 petroleum Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000001819 mass spectrum Methods 0.000 description 16
- 238000005259 measurement Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 9
- 150000002825 nitriles Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 5
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000006053 organic reaction Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CFQQTKABRMRKQY-UHFFFAOYSA-N C(C)(=O)OC.C1(=CC=CC=C1)[N+]#N Chemical class C(C)(=O)OC.C1(=CC=CC=C1)[N+]#N CFQQTKABRMRKQY-UHFFFAOYSA-N 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000012048 reactive intermediate Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- CJPVPOYTTALCNX-UHFFFAOYSA-N (2-chlorophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1Cl CJPVPOYTTALCNX-UHFFFAOYSA-N 0.000 description 1
- KEUPLGRNURQXAR-UHFFFAOYSA-N (4-chlorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(Cl)C=C1 KEUPLGRNURQXAR-UHFFFAOYSA-N 0.000 description 1
- JLIDRDJNLAWIKT-UHFFFAOYSA-N 1,2-dimethyl-3h-benzo[e]indole Chemical compound C1=CC=CC2=C(C(=C(C)N3)C)C3=CC=C21 JLIDRDJNLAWIKT-UHFFFAOYSA-N 0.000 description 1
- OGFKTAMJLKHRAZ-UHFFFAOYSA-N 2,2-dimethoxyacetaldehyde Chemical compound COC(OC)C=O OGFKTAMJLKHRAZ-UHFFFAOYSA-N 0.000 description 1
- ZCDYAMJXVAUTIM-UHFFFAOYSA-N 2-Propenyl phenylacetate Chemical compound C=CCOC(=O)CC1=CC=CC=C1 ZCDYAMJXVAUTIM-UHFFFAOYSA-N 0.000 description 1
- LDOXTQYWWYXYSQ-UHFFFAOYSA-N Butyl phenylacetate Chemical compound CCCCOC(=O)CC1=CC=CC=C1 LDOXTQYWWYXYSQ-UHFFFAOYSA-N 0.000 description 1
- NRXDHTYIDMALNV-UHFFFAOYSA-N C(C)(=O)OC.ClC1=CC=CC=C1 Chemical class C(C)(=O)OC.ClC1=CC=CC=C1 NRXDHTYIDMALNV-UHFFFAOYSA-N 0.000 description 1
- LWGLIAHUPGMJOK-UHFFFAOYSA-N CCOC(C(c1ccc(C(F)(F)F)cc1)=N)=O Chemical compound CCOC(C(c1ccc(C(F)(F)F)cc1)=N)=O LWGLIAHUPGMJOK-UHFFFAOYSA-N 0.000 description 1
- VXCUHJHWRMGYEV-UHFFFAOYSA-N CCOC(Cc1ccc(C2[IH][F]2)cc1)=O Chemical compound CCOC(Cc1ccc(C2[IH][F]2)cc1)=O VXCUHJHWRMGYEV-UHFFFAOYSA-N 0.000 description 1
- 0 Cc(cc1)ccc1S(*)(=O)=O Chemical compound Cc(cc1)ccc1S(*)(=O)=O 0.000 description 1
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- SSMBXPJYHMZLOJ-UHFFFAOYSA-N Isopropyl phenylacetate Chemical compound CC(C)OC(=O)CC1=CC=CC=C1 SSMBXPJYHMZLOJ-UHFFFAOYSA-N 0.000 description 1
- MIYFJEKZLFWKLZ-UHFFFAOYSA-N Phenylmethyl benzeneacetate Chemical compound C=1C=CC=CC=1COC(=O)CC1=CC=CC=C1 MIYFJEKZLFWKLZ-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- 238000006044 Wolff rearrangement reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- DULCUDSUACXJJC-UHFFFAOYSA-N benzeneacetic acid ethyl ester Natural products CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- OHIFNJXUDQUIBY-UHFFFAOYSA-N ethyl 3,3,3-trifluoro-2-phenylpropanoate Chemical compound CCOC(=O)C(C(F)(F)F)C1=CC=CC=C1 OHIFNJXUDQUIBY-UHFFFAOYSA-N 0.000 description 1
- PRDJGEFZGPKCSG-UHFFFAOYSA-N ethyl 3-oxo-5-phenylpentanoate Chemical class CCOC(=O)CC(=O)CCC1=CC=CC=C1 PRDJGEFZGPKCSG-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical class COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- ZQYLDVNTWDEAJI-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)acetate Chemical class COC(=O)CC1=CC=C(OC)C=C1 ZQYLDVNTWDEAJI-UHFFFAOYSA-N 0.000 description 1
- DZIQUZJSNSZOCH-UHFFFAOYSA-N methyl 2-phenylpropanoate Chemical class COC(=O)C(C)C1=CC=CC=C1 DZIQUZJSNSZOCH-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- YJMNLPRMBFMFDL-UHFFFAOYSA-N n-diazo-2-methylbenzenesulfonamide Chemical compound CC1=CC=CC=C1S(=O)(=O)N=[N+]=[N-] YJMNLPRMBFMFDL-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/12—Diazo compounds, i.e. compounds having the free valencies of >N2 groups attached to the same carbon atom
- C07C245/14—Diazo compounds, i.e. compounds having the free valencies of >N2 groups attached to the same carbon atom having diazo groups bound to acyclic carbon atoms of a carbon skeleton
- C07C245/18—Diazo compounds, i.e. compounds having the free valencies of >N2 groups attached to the same carbon atom having diazo groups bound to acyclic carbon atoms of a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing α -diazo ester compounds under normal pressure by using microwave, which takes ester compounds and p-toluenesulfonyl azide as initial raw materials, 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) as a catalyst, and can generate α -diazo ester compounds within 30min through diazo transfer reaction under microwave-assisted heating condition, and the obtained α -diazo ester compounds can further generate functional products.
Description
Technical field
The present invention relates to a kind of methods using microwave atmospheric synthesis α-diazonium ester type compound.With 2 He of ester type compound
P-toluene sulfonyt azide 3 is starting material, and 1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene (DBU) is catalyst, micro-
Under conditions of wave auxiliary heating, is reacted through a step diazo transfer, generate α-diazonium ester type compound.
Compared with the α-diazonium esters compound synthesis method reported, the present invention uses Microwave-assisted firing, organic
Reaction rate compares traditional fast several times of heating means, and reaction efficiency is high, easy to operate, synthetic reaction condition is mild, and yield exists
80-95%, product species are abundant, its functional group has diversity.The α that the present invention synthesizes-diazonium ester type compound has excellent
Chemical reactivity, can participate in Wolff rearrangement reactions, Cabbeen intercalation reaction, cyclopropyleneization reaction etc. a variety of derivatizations it is anti-
It answers, reaction condition is milder, is that one kind applies extremely wide compound.
Background technology
Microwave has been widely applied to the every field of human society as a kind of transmission medium and heating energy source, application
It is started from 1986 in the research of organic synthesis, and Gedye etc. (Tetrahedron Lett, 1986,27:279).By comparing routine
It is esterified under the conditions of condition and microwave radiation, hydrolyzes, aoxidizes etc. and reacted, found under microwave radiation, difference has been obtained by the reaction
The quickening of degree.Currently, the research of microwave assisted organic reaction has been developed as a completely new field --- MORE chemistry.
Microwave accelerates the numerous types of organic synthesis, and the substantially organic reaction that can occur under the conditions of traditional heating all may be used
To be synthesized under microwave, and have the characteristics that easy to operate, yield is high and easy purification of products.Some representative application example packets
It includes：Claisen rearrangement reactions (J.Chem.Soc., the Perkin.Trans.1992,1 of thiacyclohexane base enol:311), 2- methyl-
1,3- cyclopentadienyls diene reacts (Tetrahedron Lett.1991,32 with the Diels-Alder of dimethoxy acetaldehyde:1723), saccharin
With the alkylated reaction (Synth.Commun.1994,24 of bromoalkane:301).In addition, diazonium ester type compound is one kind to α-has
Machine synthesis in apply extremely wide reactive intermediate, have good chemo-selective (Chem.Rev.2015,115:
9981).Common traditional synthesis α-diazonium ester type compound mainly by feeding intake at low temperature, the method being stirred overnight at room temperature
It is synthesized.Reported in literature yet there are no using microwave normal pressure one-step synthesis α-diazonium ester type compound.
The present invention utilizes microwave atmospheric synthesis technology, is with commercially available ester type compound 2 and p-toluene sulfonyt azide 3
Raw material, 1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene (DBU) is catalyst, under conditions of Microwave-assisted firing, warp
One step diazo transfer reacts, and has synthesized a series of α-diazonium ester compounds 1 of different structures.
Invention content
It is an object of the invention to utilize microwave atmospheric synthesis technology, with commercially available ester type compound 2 and to toluene
Sulfonyl azide 3 is raw material, and 1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene (DBU) is catalyst, and a step is realized intermolecular
Diazo transfer reacts, and synthesizes and applies extremely wide reactive intermediate α-diazonium ester type compound in organic synthesis.
To achieve the goals above, technical scheme is as follows：
With 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU) be catalyst, set microwave reactor power,
Heating temperature, heating time carry out intermolecular diazo transfer reaction (reaction equation 1) in acetonitrile solvent.It presses after reaction normal
It advises isolation and purification method and carries out product separation and characterization, obtain α-diazonium ester type compound 1.
Technical solution is characterized in that：
1. ester type compound 2 and p-toluene sulfonyt azide 3 are raw material, its substituent group of ester type compound 2 is：R1Selected from following
Group：The phenyl of ethyl, acetyl group or halogen, trifluoromethyl, methyl, methoxyl group and p-toluenesulfonyl substitution；R2For carbon original
Subnumber is alkyl, allyl or the benzyl of 1-4.
2. catalysts are triethylamine, pyridine, triethylene diamine (DABCO), 1,5- diazabicyclos [4.3.0] nonyl-
5- alkene (DBN), 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU), 4-dimethylaminopyridine (DMAP), wherein 1,8-
Diazabicyclo [5.4.0] 11 carbon -7- alkene (DBU) effect is best.
3. reaction dissolvent is acetonitrile, toluene, 1,4- dioxane, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO)
(DMSO) one kind in；Wherein, reaction effect in aprotic polar solvent acetonitrile is best.
4. the molar concentration of ester type compound 2 is 0.05-1.0M, optimal is 0.1M.
5. the reaction time is 20-60min.Wherein, optimum reacting time 30min.
6. microwave reactor sets power as 200-800W, reaction temperature is 30-60 DEG C.Wherein, it is best set power as
400W, optimal reaction temperature are 30 DEG C.
The present invention has the following advantages：
1) α -1 synthetic reaction of diazonium ester type compound takes short, reaction efficiency under conditions of normal pressure microwave assists heating
Height, mild condition, product yield high can reach 95% separation yield.
2) raw material ester type compound 2 has structure diversity, can be used for synthesizing α-diazo ester of different type and structure
Compound 1.
3) 3 commercially available of raw material ester type compound 2 and p-toluene sulfonyt azide is easy to prepare, and it is cheap and easily-available to prepare raw material,
It is of low cost, it is easy to industrialized production.
4) synthetic reaction of α-diazonium ester type compound 1 uses the 1,8- diazabicyclos of the relatively low relative nontoxic of price
[5.4.0] 11 carbon -7- alkene (DBU) is used as catalyst, environmentally friendly, and can be convenient for product in ammonium chloride solution at salt
Isolate and purify.
5) functional group's diversity that α -1 product of diazonium ester type compound has had, it is with a wide range of applications.
6) α -1 product of diazonium ester type compound has excellent chemical reactivity, can be used for a variety of derivative reactions, this
Product can be as drug and the intermediate of chemical products.
In short, the present invention utilizes microwave atmospheric synthesis technology, with commercially available p-toluene sulfonyt azide 3 and various structures
Ester type compound 2 efficiently synthesize different types of α-diazonium ester type compound 1, raw material is cheap and easily-available, takes short, reaction effect
Rate is high, easy to operate, and target product yield is high, and can further derivatization.
Specific implementation mode
Contribute to further understand the present invention by following embodiments, but present disclosure is not limited to that.
Embodiment 1
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, methyl phenylacetate 2a (10.0mmol) and 20mL acetonitriles is added,
P-toluene sulfonyt azide 3a (11.0mmol) is added, is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU)
(15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 400W, 30 DEG C of heating temperature, when heating
Between 30min, open exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched, dichloro
Methane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel column layer
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 for analysis separation:1) Red oil target product 1a, is obtained
(1.67g, yield 95%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 2
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, o-fluoro-acid methyl esters 2b (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 700W, and 60 DEG C of heating temperature adds
Hot time 30min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80 to column chromatography for separation:1) yellow oily target product 1b, is obtained
(1.55g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 3
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, o-chlorobenzene acetic acid methyl esters 2c (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 700W, and 40 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) yellow oily target product, is obtained
1c (1.81g, yield 86%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 4
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, chlorophenyl acetate 2d (10.0mmol) and 20mL second between addition
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 600W, and 40 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) yellow oily target product, is obtained
1d (1.75g, yield 83%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 5
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, p-chlorophenyl acetate 2e (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 500W, and 40 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) yellow oily target product, is obtained
1e (1.68g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 6
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, are added to methylphenyl acetic acid methyl esters 2f (10.0mmol) and 20mL
Acetonitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 600W, and 60 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) red solid target product, is obtained
1f (1.62g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 7
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, be added homoanisic acid methyl esters 2g (10.0mmol) and
20mL acetonitriles are added p-toluene sulfonyt azide 3a (11.0mmol), are slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon-
7- alkene (DBU) (15.0mmol) stirs 5 minutes under ice bath, is put into microwave reactor, sets power 400W, heating temperature 40
DEG C, heating time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and carries out
It is quenched, dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, depressurizes lower removing Volatile Colstituent, then
With silica gel column chromatography separation, (eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100:1) red solid mesh, is obtained
Mark product 1g (1.75g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 8
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, p-hydroxyphenylaceticacid methyl esters 2h (10.0mmol) and 20mL is added
Acetonitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 200W, and 40 DEG C of heating temperature adds
Hot time 60min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) yellow solid target product, is obtained
1h (2.60g, yield 75%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 9
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, be added to trifluoromethyl phenylacetic acid ethyl ester 2i (10.0mmol) and
20mL acetonitriles are added p-toluene sulfonyt azide 3a (11.0mmol), are slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon-
7- alkene (DBU) (15.0mmol) stirs 5 minutes under ice bath, is put into microwave reactor, sets power 400W, heating temperature 40
DEG C, heating time 60min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and carries out
It is quenched, dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, depressurizes lower removing Volatile Colstituent, then
With silica gel column chromatography separation, (eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80:1) red solid target, is obtained
Product 1i (2.06g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 10
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, ethyl phenylacetate 2j (10.0mmol) and 20mL acetonitriles is added,
P-toluene sulfonyt azide 3a (11.0mmol) is added, is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU)
(15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 400W, 40 DEG C of heating temperature, when heating
Between 40min, open exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched, dichloro
Methane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel column layer
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 for analysis separation:1) yellow oily target product 1j, is obtained
(1.62g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 11
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, Isopropyl phenylacetate 2k (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 300W, and 40 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80 to column chromatography for separation:1) yellow oily target product 1k, is obtained
(1.73g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 12
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, phenylacetic acid allyl ester 2l (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 400W, and 40 DEG C of heating temperature adds
Hot time 40min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 to column chromatography for separation:1) yellow oily target product, is obtained
1l (1.62g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 13
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, butyl phenylacetate 2m (10.0mmol) and 20mL acetonitriles is added,
P-toluene sulfonyt azide 3a (11.0mmol) is added, is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU)
(15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 600W, 40 DEG C of heating temperature, when heating
Between 50min, open exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched, dichloro
Methane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel column layer
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=100 for analysis separation:1) yellow oily target product 1m, is obtained
(1.75g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 14
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, benzyl phenylacetate 2n (10.0mmol) and 20mL acetonitriles is added,
P-toluene sulfonyt azide 3a (11.0mmol) is added, is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU)
(15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 800W, 20 DEG C of heating temperature, when heating
Between 60min, open exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched, dichloro
Methane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel column layer
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80 for analysis separation:1) yellow solid target product 1n, is obtained
(2.02g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 15
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, ethyl acetoacetate 2o (10.0mmol) and 20mL second is added
Nitrile is added p-toluene sulfonyt azide 3a (11.0mmol), is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene
(DBU) (15.0mmol) is stirred 5 minutes under ice bath, is put into microwave reactor, sets power 400W, and 40 DEG C of heating temperature adds
Hot time 20min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and is quenched,
Dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, is depressurized lower removing Volatile Colstituent, is then used silica gel
(eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80 to column chromatography for separation:1) yellow oily target product 1o, is obtained
(1.33g, yield 85%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 16
Two mouthfuls of reaction bulbs of 100mL are placed in 0 DEG C of ice bath, be added 2- ethyl benzylacetoacetates 2p (10.0mmol) and
20mL acetonitriles are added p-toluene sulfonyt azide 3a (11.0mmol), are slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon-
7- alkene (DBU) (15.0mmol) stirs 5 minutes under ice bath, is put into microwave reactor, sets power 400W, heating temperature 50
DEG C, heating time 30min opens exhaust fan.After reaction, mixture is cooled to room temperature, ammonium chloride solution is added and carries out
It is quenched, dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, depressurizes lower removing Volatile Colstituent, then
With silica gel column chromatography separation, (eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80:1) yellow oily target, is obtained
Product 1p (1.63g, yield 80%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Embodiment 17
Example 1 is compared with preparation α-diazonium ester compounds under traditional reaction condition.Two mouthfuls of reaction bulbs of 100mL are set
In 0 DEG C of ice bath, methyl phenylacetate 2a (10.0mmol) and 20mL acetonitriles is added, p-toluene sulfonyt azide 3a is added
(11.0mmol) is slowly added to 1,8- diazabicyclos [5.4.0], 11 carbon -7- alkene (DBU) (20.0mmol), is stirred under ice bath
It mixes 5 minutes, removes ice bath, stirring.Take two timing nodes of 30min and 10h respectively, in reaction solution be added ammonium chloride solution into
Row is quenched, and dichloromethane is extracted with water, collection organic phase, anhydrous sodium sulfate drying, filtering, depressurizes lower removing Volatile Colstituent, so
With silica gel column chromatography separation, (eluent is petroleum ether (60-90 DEG C)/ethyl acetate, v/v=80 afterwards:1) yellow oily mesh, is obtained
Mark product.Comparative example 1 and the reaction yield that α-diazo ester is prepared under the conditions of reaction equation (18), (19), (20), find
Under conditions of reaction equation (18), the yield of 30min is only capable of reaching 15%, and raw material 2a is largely remaining；Condition in reaction equation (19)
Under, the yield of 30min is only capable of reaching 20%；Under conditions of reaction equation (20), the yield of 30min is only capable of reaching 35%, and
Under microwave condition, the yield of 30min is 95%, and raw material 2a is completely consumed；In addition, 10h is reacted under conditions of reaction equation (20),
Yield is 85%, is still unable to reach 95%, and raw material 2a does not have residue.It can be seen that reaction time consumption is longer under conventional conditions, instead
Answer inefficient, temperature is excessively high to cause raw material decomposes rotten, cannot be converted to target product；It can illustrate only to increase simultaneously anti-
Temperature is answered, microwave irradiation is not given, can not realize rapidly and efficiently preparing for α-diazonium ester type compound in a short time.
Embodiment 18
Under conditions of embodiment 1, the basic catalyst used in reaction is compared.It is quenched after reaction 20min anti-
It answers, isolates and purifies to obtain target product.It was found that reaction equation (2) uses 11 carbon -7- alkene of 1,8- diazabicyclos [5.4.0]
(DBU) it is catalyzed, yield 95%；Reaction equation (19) uses triethylamine (EtN3) it is used as catalyst, yield 75%；Reaction equation (20)
Catalyst, yield 73% are used as using 4-dimethylaminopyridine (DMAP)；Reaction equation (21) uses 1,5- diazabicyclos
[4.3.0] nonyl- 5- alkene (DBN) is used as catalyst, yield 78%.As it can be seen that 1,8- diazabicyclo [5.4.0], 11 carbon -7-
Alkene (DBU) can better compatible with microwave environment, reach best reaction effect.
Typical compound characterize data
Phenyldiazonium acetic acid methyl ester derivatives (1a), red oil.1H NMR(400MHz,CDCl3)δ7.49(dd,J
=8.5,1.1Hz, 2H), 7.43-7.35 (m, 2H), 7.23-7.14 (m, 1H), 3.87 (s, 3H)
Phenyldiazonium acetic acid methyl ester derivatives (1i), red oil.1H NMR(400MHz,CDCl3)δ7.62(d,J
=8.1Hz, 4H), 4.35 (q, J=7.1Hz, 2H), 1.35 (t, J=7.1Hz, 3H).
Claims (7)
1. a kind of method using microwave atmospheric synthesis α-diazonium ester type compound, α-diazonium esters molecular structure of compounds formula is such as
Under：
R1Selected from following group：What ethyl, acetyl group or halogen, trifluoromethyl, methyl, methoxyl group and p-toluenesulfonyl replaced
A kind of to seven kinds in phenyl, number is 1-7；R2Alkyl, allyl or the benzyl for being 1-4 for carbon atom number；
It is starting material, 1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene with ester type compound 2 and p-toluene sulfonyt azide 3
(DBU) it is catalyst, under conditions of Microwave-assisted firing, diazo transfer reaction occurs, a step generates α-diazonium esters chemical combination
Object 1；
The molecular structural formula of ester type compound 2 and p-toluene sulfonyt azide 3 is as follows,
R1Selected from following group：What ethyl, acetyl group or halogen, trifluoromethyl, methyl, methoxyl group and p-toluenesulfonyl replaced
Phenyl；R2Alkyl, allyl or the benzyl for being 1-4 for carbon atom number.
2. according to the method for claim 1, it is characterised in that：
Synthetic route as shown in following reaction equations,
3. according to method as claimed in claim 1 or 2, it is characterised in that：
The molar ratio of ester type compound 2 and p-toluene sulfonyt azide 3 is 1:1-1:2；
Catalyst be triethylamine, pyridine, triethylene diamine (DABCO), 1,5- diazabicyclos [4.3.0] nonyl- 5- alkene (DBN),
1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene (DBU), the one or two or more kinds in 4-dimethylaminopyridine (DMAP),
The molar ratio of ester type compound 2 and catalyst is 1:0.5-1:5；
Reaction dissolvent is in acetonitrile, toluene, 1,4- dioxane, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) (DMSO)
One or two or more kinds；Molar concentration of the ester type compound 2 in reaction dissolvent is 0.05-1.0M；
Reaction atmosphere is normal pressure air；Reaction time is 20-60min；Microwave reaction temperature is 30-60 DEG C；Set power as
200-800W。
4. synthetic method described in accordance with the claim 3, it is characterised in that：Ester type compound 2 is excellent with p-toluene sulfonyt azide 3
It is 1 to select molar ratio:1.1.
5. according to the method for claim 3, it is characterised in that：Ester type compound 2 generates in 1 reaction 2 with catalyst
Preferred molar ratio is 1:1.5.
6. according to the method for claim 3, it is characterised in that：The reaction of the generation of ester type compound 21 is preferably in non-proton pole
It is carried out in property solvent acetonitrile.
7. according to the method for claim 3, it is characterised in that：In the reaction of the generation of ester type compound 21, the reaction time is
30min, microwave reactor set power as 400W, and reaction temperature is 30 DEG C.
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Application publication date: 20181102 |